In Vivo Yeast Cell Morphogenesis Is Regulated by a p21-Activated Kinase in the Human Pathogen Penicillium marneffei

Pathogens have developed diverse strategies to infect their hosts and evade the host defense systems. Many pathogens reside within host phagocytic cells, thus evading much of the host immune system. For dimorphic fungal pathogens which grow in a multicellular hyphal form, a central attribute which facilitates growth inside host cells without rapid killing is the capacity to switch from the hyphal growth form to a unicellular yeast form. Blocking this transition abolishes or severely reduces pathogenicity. Host body temperature (37°C) is the most common inducer of the hyphal to yeast transition in vitro for many dimorphic fungi, and it is often assumed that this is the inducer in vivo. This work describes the identification and analysis of a new pathway involved in sensing the environment inside a host cell by a dimorphic fungal pathogen, Penicillium marneffei. The pakB gene, encoding a p21-activated kinase, defines this pathway and operates independently of known effectors in P. marneffei. Expression of pakB is upregulated in P. marneffei yeast cells isolated from macrophages but absent from in vitro cultured yeast cells produced at 37°C. Deletion of pakB leads to a failure to produce yeast cells inside macrophages but no effect in vitro at 37°C. Loss of pakB also leads to the inappropriate production of yeast cells at 25°C in vitro, and the mechanism underlying this requires the activity of the central regulator of asexual development. The data shows that this new pathway is central to eliciting the appropriate morphogenetic response by the pathogen to the host environment independently of the common temperature signal, thus clearly separating the temperature- and intracellular-dependent signaling systems

On the finite generation of valuation semigroups on toric surfaces

We provide a combinatorial criterion for the finite generation of a valuation semigroup associated with an ample divisor on a smooth toric surface and a non-toric valuation of maximal rank. As an application, we construct a lattice polytope such that none of the valuation semigroups of the associated polarized toric variety coming from one-parameter subgroups and centered at a non-toric point are finitely generated.Comment: 28 pages, 13 figures, minor corrections, revision of section

Power considerations towards a sustainable pan-european network

Energy savings are observed and quantified in the Pan-European network using transparent optical network technology. The network was dimensioned, using realistic traffic predictions of the optical networking roadmap of the European project BONE

The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae

AbstractBackground: Following chromosome segregation in anaphase, ubiquitin-dependent degradation of mitotic cyclins contributes to the exit from mitosis. A key step in this process is catalyzed by a ubiquitin–protein ligase known as the anaphase-promoting complex (APC), the regulation of which is poorly understood. The Polo-related protein kinase Cdc5 in Saccharomyces cerevisiae might encode a regulator of the APC, because cdc5 mutant cells arrest with a late mitotic phenotype similar to that observed in cells with defective cyclin destruction.Results: We investigated the role of Cdc5 in the regulation of mitotic cyclin degradation. In cdc5-1 mutant cells, we observed a defect in the destruction of cyclins and a reduction in the cyclin–ubiquitin ligase activity of the APC. Overexpression of CDC5 resulted in increased APC activity and mitotic cyclin destruction in asynchronous cells or in cells arrested in metaphase. CDC5 mutation or overexpression did not affect the degradation of the APC substrate Pds 1, which is normally degraded at the metaphase-to-anaphase transition. Cyclin-specific APC activity in cells overexpressing CDC5 was reduced in the absence of the APC regulatory proteins Hct 1 and Cdc20. In G1, Cdc5 itself was degraded by an APC-dependent and Hct1-dependent mechanism.Conclusions: We conclude that Cdc5 is a positive regulator of cyclin-specific APC activity in late mitosis. Degradation of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its activator at the onset of the next cell cycle

Non-destructive extraction of junction depths of active doping profiles from photomodulated optical reflectance offset curves

The ITRS Roadmap highlights the electrical characterization of the source and drain extension regions as a key challenge for future complimentary-metal-oxide-semiconductor technology. Presently, an accurate determination of the depth of ultrashallow junctions can routinely only be performed by time-consuming and destructive techniques such as secondary ion mass spectrometry (SIMS). In this work, the authors propose to use the fast and nondestructive photomodulated optical reflectance (PMOR) technique , as implemented in the Therma-Probe\textregistered (TP) dopant metrology system, for these purposes. PMOR is a pump-probe technique based on the measurement of the pump-induced modulated change in probe reflectance, i.e., the so-called (photo) modulated reflectance. In this article, the authors demonstrate that the absolute junction depths of boxlike active dopant structures can be extracted in a very simple and straightforward way from the TP offset curves, which represent the behavior of the modulated reflectance as a function of the pump-probe beam spacing. Although the procedure is based on the insights into the physical behavior of the offset curves, no modeling is involved in the actual extraction process itself. The extracted junction depths are in good correlation with the corresponding junction depths as measured by means of SIMS. The technique has a subnanometer depth sensitivity for depths ranging from 10 to 35 nm with the present Therma-Probe\textregistered 630XP system. The extension of the proposed procedure to the general ultrashallow profiles is also explored and discusse

2017 Robotic Instrument Segmentation Challenge

In mainstream computer vision and machine learning, public datasets such as ImageNet, COCO and KITTI have helped drive enormous improvements by enabling researchers to understand the strengths and limitations of different algorithms via performance comparison. However, this type of approach has had limited translation to problems in robotic assisted surgery as this field has never established the same level of common datasets and benchmarking methods. In 2015 a sub-challenge was introduced at the EndoVis workshop where a set of robotic images were provided with automatically generated annotations from robot forward kinematics. However, there were issues with this dataset due to the limited background variation, lack of complex motion and inaccuracies in the annotation. In this work we present the results of the 2017 challenge on robotic instrument segmentation which involved 10 teams participating in binary, parts and type based segmentation of articulated da Vinci robotic instruments

Reaching out to early-career astrobiologists: AbGradE's actions and perspectives

Astrobiology Graduates in Europe (AbGradE, pronounced ab-grad-ee) is an association of early-career scientists working in fields relevant to astrobiological research. Conceptualized in 2013, it was initially designed as a mini-conference or workshop dedicated to early-career researchers, providing a friendly environment where early-career minds would be able to present their research without being intimidated by the possibility of facing a more traditional audience, composed mainly of senior scientists. Within the last couple of years, AbGradE became the first point of call for European, but also for an increasing number of non-European, early-career astrobiologists. This article aims to present how AbGradE has evolved over the years (in its structure and in its way of organizing events), how it has adapted with the COVID-19 pandemic, and what future developments are considered